Genetic Changes Increase Girls’ Bone Density?

Researchers from The Children’s Hospital of Philadelphia (CHOP) have found that rare genetic changes strongly increase the likelihood that girls will have higher bone density.

“We investigated whether the same gene variants that strongly affect bone density in adults also affected bone density in children, ” said co-first author Jonathan A. Mitchell, Ph.D., a pediatric growth researcher and Instructor of Pediatrics at CHOP, in the March 23, 2016 news release. “We found the effect was even stronger in children, but only in girls. The effect may exert lifetime impacts on bone health.” Alessandra Chesi, Ph.D., a genetics researcher at CHOP, was the other co-first author.

As indicated in the news release, “The study team, co-led by senior authors Babette S. Zemel, Ph.D., and Struan F.A. Grant, Ph.D., analyzed a cohort of 1, 418 children and adolescents—733 girls and 685 males, all of European ancestry, who were part of a larger study group, the Bone Mineral Density in Childhood Study. The researchers focused on rare variants near the gene EN1, because researchers led by a group at McGill University had discovered that this site showed strong effects on increasing bone density in a landmark 2015 whole-genome sequencing study in adults. The researchers found that rare variants near the EN1 gene were indeed the strongest variants to date found in children, but only in females. The study team noted that follow-up research needs to be done to replicate these findings.”

“In addition, functional studies should investigate how the same genetic variants have different effects in males and females, ” said Dr. Grant. “For instance, ” he added, “sex-specific differences in circulating sex hormones and other signaling molecules may play a role in altering bone.”

Dr. Mitchell told OTW, “A team of investigators recently discovered rare genetic variants near EN1 that associated with higher bone mineral density (BMD) in adults and the effect sizes were strikingly large. We were interested in testing if the same rare variants associated with pediatric BMD. Childhood is a key developmental period when bone is being accrued. Greater gains in BMD before peak bone mass is achieved may lower the risk of bone fragility in later life. It is therefore important to know if the skeleton is under the same genetic regulation at all developmental stages.”

“We found that the lead rare variant near EN1 associated with pediatric BMD. Importantly, the direction of association matched that observed in adults and the effect size in the pediatric setting was also strikingly large. Furthermore, we found a sex difference with the association only seen in females and this was particularly interesting given the higher prevalence of osteoporosis and fracture observed among adult women.”

“Rare variants near EN1 are associated with higher BMD across the lifespan. Further research is needed to fully understand the biological implication of these findings but our pediatric results point to an early life genetic mechanism for the risk of osteoporosis and fracture in later life.”